The development of the humoral immune system will be evaluated in animal models where there is evidence for genetically-determined abnormalities. These include: autoimmune NZB, BXSB, and MRL/Lpr; immunodeficient CBA/N; autoinuune/immunodeficient motheaten; and stem cell deficient W/W mice. Cell separation, transfer, and culture methods as well as monoclonal antibodies to cell surface antigens are now available for identifying, enumerating, and manipulating several types of B lineage-precursor cells. Preliminary observations indicate that it may be possible to localize particular defects in these models and attribute them to differentiating B ormicroenvironmental cells. The studies will then be extended with investigations concerning the kinetics of formation of B cells and their precursors. The discovery of a conserved antigen shared by the lymphoid cells of mouse and man should make it feasible to extend certain of these findings to an analysis of patients with immunodeficiency or immunoregulatory diseases.